Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients aged ≥60 years (EXTEND): analysis of cost-effectiveness

Abstract

Objectives: The randomized Phase IIIb/IV EXTEND trial showed that extended-pulsed fidaxomicin significantly improved sustained clinical cure and reduced recurrence versus vancomycin in patients ≥60 years old with Clostridium difficile infection (CDI). Cost-effectiveness of extended-pulsed fidaxomicin versus vancomycin as first-line therapy for CDI was evaluated in this patient population.

Methods: Clinical results from EXTEND and inputs from published sources were used in a semi-Markov treatment-sequence model with nine health states and a 1 year time horizon to assess costs and QALYs. The model was based on a healthcare system perspective (NHS and Personal Social Services) in England. Sensitivity analyses were performed.

Results: Patients receiving first-line extended-pulsed fidaxomicin treatment had a 0.02 QALY gain compared with first-line vancomycin (0.6267 versus 0.6038 QALYs/patient). While total drug acquisition costs were higher for extended-pulsed fidaxomicin than for vancomycin when used first-line (£1356 versus £260/patient), these were offset by lower total hospitalization costs (which also included treatment monitoring and community care costs; £10 815 versus £11 459/patient) and lower costs of managing adverse events (£694 versus £1199/patient), reflecting the lower incidence of CDI recurrence and adverse events with extended-pulsed fidaxomicin. Extended-pulsed fidaxomicin cost £53 less per patient than vancomycin over 1 year. The probability that first-line extended-pulsed fidaxomicin was cost-effective at a willingness-to-pay threshold of £30 000/QALY was 76% in these patients.

Conclusions: While fidaxomicin acquisition costs are higher than those of vancomycin, the observed reduced recurrence rate with extended-pulsed fidaxomicin makes it a more effective and less costly treatment strategy than vancomycin for first-line treatment of CDI in older patients.

Figures

Figure 1.

Overview of clinical pathway used in the semi-Markov model. Hypothetical patients entered the model in the ‘initial CDI episode’ health state and received either EPFX or vancomycin, with possible outcomes of ‘clinical response’, ‘treatment failure’, or ‘death’. Patients in the ‘clinical response’ state were considered to be at risk of CDI recurrence for ≤90 days after treatment initiation: up to two recurrence episodes were permitted. If a recurrence occurred, patients transitioned to the (first or second) ‘CDI recurrence’ state and received treatment, whereas if no recurrence occurred within 90 days, patients moved to a ‘disease-free survival’ state, where they either remained or moved to the ‘death’ state. Patients who had treatment failure initiated another course of therapy, with the same possible outcomes of ‘clinical response’, ‘treatment failure’, or ‘death’. Those failing the second course of therapy received a third course (rescue therapy) and transitioned either to ‘death’ or ‘clinical response’ followed by the ‘disease-free survival’ state after 90 days, as third-line therapy was assumed to provide 100% response with no risk of further recurrences to keep the model tractable. CDI, Clostridium difficile infection; EPFX, extended-pulsed fidaxomicin.

Figure 2.

Model inputs and outputs relating to (a) Clostridium difficile infection recurrence and relative risk of recurrence and (b) costs (base-case analysis). EPFX, extended-pulsed fidaxomicin; RR, relative risk. An asterisk indicates P < 0.001 according to the Cochran–Mantel–Haenszel test adjusted for stratification factors.

Figure 3.

Model cost-effectiveness plane (base-case analysis). A cost-effectiveness plane consists of four quadrants, where the x-axis represents the incremental level of effectiveness of a new intervention (first-line EPFX in the present model) and the y-axis represents the additional total cost of introducing the new intervention. Standard of care (first-line vancomycin in the current model) occupies the origin of the graph. Depending on the incremental cost-effectiveness ratio, the new intervention will be located to the right or left of the origin if it is more or less effective than standard of care and above or below the origin if it is more or less costly. When a new intervention is both clinically superior and cost saving, it is referred to as an economically ‘dominant’ strategy. The opposite is a ‘dominated’ strategy. EPFX, extended-pulsed fidaxomicin.

Figure 4.

Probabilistic sensitivity analysis: cost-effectiveness acceptability curve. EPFX, extended-pulsed fidaxomicin.